Obstructive sleep apnea (OSA) occurs in 5-20% of the adult population. The pathophysiology of OSA is multifactorial and includes impaired upper airway anatomy, low arousal threshold, respiratory control instability, and/or altered neuro-muscular control of upper airway muscles. A validated method has been pioneered by Wellman and Sands to calculate the relative contribution of each of these components from diagnostic polysomnography and this approach may define pathophysiologic phenotypes of the syndrome. We and others have shown that WTC dust-exposed subjects have a high prevalence of conditions such as chronic rhinosinustis, gastroesophageal reflux disease, post-traumatic stress disorder and obesity that increase risk for OSA. Our goal is to define how these comorbid conditions might act via individual pathophysiologic mechanisms defined as a ?phenotype of OSA.? Our current data in over 600 WTC responders shows an extraordinary prevalence of OSA of 75 %. We have also found an association between new or worsening chronic rhinosinusitis (CRS) symptoms since 9/11 and OSA that is significant even after controlling for known risk factors for OSA such as age, gender and BMI. This association is not explained by increased nasal resistance in those with CRS, suggesting other mechanisms could impact upper airway function in CRS including neuropathy, fibrosis and reduced upper airway sensitivity that impairs mechanoreflexes to negative pressure. We propose that an impaired afferent limb of upper airway reflexes impairs the ability to perceive and/or process upper airway loading and contributes to failure of upper airway stiffening. Furthermore, the high prevalence of OSA even in subjects without CRS highlights the need to identify the mechanisms of OSA in these subjects. The aims of this proposal are to 1. Examine the mechanism by which CRS increases the risk for OSA. Building on our previous findings of increased prevalence of OSA in subjects with CRS symptoms, we will examine the role of sensory function (2-point discrimination and vibration sensitivity threshold) in the upper airway in four groups of 50 subjects each with and without OSA and with and without CRS. 2. Examine the relationship of the mechanistic OSA phenotype components to CRS in WTC responders. In 100 subjects diagnosed with OSA (50 with CRS and 50 without CRS) we will test if upper airway muscle compensation is lower in subjects with CRS. 3. Examine differences in the distribution of OSA pathophysiologic phenotypes between WTC responders and matched patients from a sleep clinic population without exposure to WTC dust. In 100 subjects in each group we will test the hypothesis that WTC subjects have a greater proportion of subjects with a) mild UA collapsibility b) low arousal threshold and c) low muscle compensation compared to non-WTC subjects. This proposal will provide insight into the pathophysiologic mechanisms and mechanistic components of OSA in WTC Responders, which could help identify groups responding to non-PAP therapies and contribute to a more rational approach to developing and combining non-CPAP therapies.